Dimethyl-cyclopentano-polyhydrophenanthrene compounds and process of making same



Patented May 11, 1,943

DME THYL-CYCLOPENTANO POLYHYDRO- PHENANTHRENE COMPOUNDS AND PROC- ESS OF MAKING SAME Karl Miescher, Riehen, and Albert Wettstein,

Basel, Switzerland, assignors to Ciba Pharmaceutical Products, Incorporated, Summit, N. J a corporation of New Jersey No Drawing. Original application December 20,

1940, Serial No. 371,058. Divided and this application July 31, 1942, Serial No; 453,098. In Switzerland December 19, 1939 Claims.

It is known that saturated or unsaturated substituted polynuclear ring-ketones may be obtained by the following process: Nuclear saturated or unsaturated sterols or bile acids, their derivatives or degradation products, containing secondary nuclear hydroxyl groupsparticularly in 3-position-as well as, if desired, nuclear double bonds protected from the oxidizing action, the former by substitution and the latter by temporary saturation, are treated with oxidizing agents, the poly-nuclear ring-ketones are reof the dimethyl-eyelopentanoepolyhydrophenanthrene series surprisingly may also be obtained if compounds of the said series containing any ,desired side chain in 17-position and, in rings A and B, ,merely carbon double bonds and/or free or fsubstitutedtertiary hydroxyl groups, are treated with oxidizing agents, such as chromic acid, permanganates, peroxides, lead tetracylates, and the like, if desired, with temporary protection .Of,nucleardoubl bonds which may bev present, or if the oxidation, is carried out by electrical means and/or with oxygenin the presence of oxygen barriers, such as lead peroxide or vanadic acid, ,and if the resulting non-volatile products, formed by the complete or partial degradation of the side chain, 'ar removed from the oxidation mixture. 'I'o'the oxidation mixture furthermore compounds catalyzing the oxidation-may be added, for example halogens or strong inorganic acids, such as sulphuric acids or perchloric acid. The temporary protection of nuclear double bonds is effected, if desired, for example by addition of hale ogen or hydrogen halide. After the oxidation, in order to re-establish the double bonds, agents which split ofi halogen or hydrogen halide are then allowed to act upon the oxidation products in any desired purifying stage. Such agents are, for example, zinc dust and acetic acid, zinc dust and methanol, alkali-iodides, or catalytically excited hydrogen on the one hand, or tertiary bases, such as pyridine, dimethylaniline, as Well as car-, boxylic acid salts or alkalis on the other. It is also possible to carryout the reaction without the protection of the nuclear double bonds, but in this case, in addition to the degradation of the side chain, oxygenmay enter into the rings A and/or B. Thus, by use of chromic acid as oxidizing agent, compounds, for example, with'azfl-unsaturated ketone groupings in the rings mentioned may be obtained.

The carboxylic acids resulting from partial oxidative degradation of the side chains, the car-. boxylic group of which is to be found in the side chain or in place of this latter, can be obtained from the oxidation mixture, for example in the form of their salts,'with' the help of alkaline substances, and the liberated free acids purifieda'nd isolated, for example, again by way of their salts and/or by recrystallization, by preparation of es .of physical and/or chemical methods, for example, by use of ketone reagents, by fractional crystallization, adsorption, by high vacuum sublimation, andthe like. As ketone reagents, use is preferably made of hydrazine or hydroxylamine,

oholestane-20-one of Formula V, and 5-chloronorcholestane25-one of Formula VI.

CHa CHI III CH; CH:

CO-OHs A I b Y CH; C H;

The salt of a basically substituted acetyl hydrazine may be-equally well replaced by other ketone reagents, such as semicarbazide acetate. It is also possible to make use of other purifying or group, for example, a bromine atom, an acyloxy or an alkoxy group, correspondingly substituted end products are obtained. They may all be converted into unsaturated compounds by means of the action of agents which split 01? acid, alcohol or phenol, for example, by the action of agents which split ofi hydrogen halide.

On the other hand, if, for example, 5-hydroxycholestane, 5-hydroxy-sitostane or 5-hydroxystigmastene (obtained, for instance, from the 4:5- or 5:6-unsaturated compounds by the action of per-phthalic or per-benzoic acid and catalytic hydrogenation) be used as parent substance, the corresponding 5-hydroxy derivatives are obtained. By the action of agents which split ofl water, these may be converted into the corresponding unsaturated compounds.

The oxidation described may also be carried out after addition of halogen, such as chlorine or bromine, or of strong inorganic acids for example, sulphuric acid or perchloric acid; in such cases often particularly good yields are obtained.

The present applicaiton is a division of applicants prior application Ser. No. 371,058, filed December 20, 1940.

What we claim is:

1. The dimethyl-cyclopentano-polyhydrophenanthrene compounds containing in 17-position an oxo group and in the rings A and B only a member of the group consisting of a tertiary hydroxyl group and a group which upon hydrolysis is converted into a tertiary hydroxyl group.

2. The dimethyl cyclopentano-polyhydrophenanthrene compounds containing in 17-position an oxo group and in the rings A and B only a free hydroxyl group in 5-position.

3. The dimethyl cyclopentano-polyhydrophenanthrene compounds containing in 17-position an oxo group and in the rings A and B only a halogen atom in 5-position.

4. The dimethyl cyclopentano-polyhydrophenanthrene compounds containing in I'Z-position an oxo group and in the rings A and B only a chlorine atom in 5-position.

5. The S-chIoro-androstane-17 one of the formula:

CH: CH3

l IT" \/cl\/ KARL MIESCHER. ALBERT WETTSTEIN. 

